Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of Application/Election/Restrictions
Applicant's election with traverse of Group I (claims 1-10 and 34), miRNA for species of molecule, miRNA-21 for species of miRNA, AAV1 for species of AAV, astrocytes for species of protein and cells, rabies virus glycoprotein (RVG) for species of genetically modified protein or fragment thereof and traumatic peripheral nerve injury for species of disease in the reply filed on November 12, 2025 is acknowledged. The traversal is on the ground(s) that multiple groups can be searched without undue burden. This is not found persuasive because based on PCT rule 13.1, Applicant's inventions lack unity of invention. As previously made of record, a composition comprising a glial-derived extracellular vesicle recited in claim 1 is not a special technical feature in view of Pusic et al. (US2019/0160097; see para.[0014];[0016]; [0023]-[0030]; [0085]; [0099]-[0105) or Hyung et al. (see p. 156; Immunotherapy; published Sep 18, 2019; 5:156. doi:10.35248/2471-9552.19.5.156) or Kim (see p. 7-8; Kim, MS Thesis, University of Minnesota, May 2018). Therefore, claim 1 is anticipated by Pusic, Hyung or Kim. Since the 1st claimed invention has no special technical feature, it cannot share a special technical feature with the other claimed inventions. Thus, Applicant’s inventions do not contribute a special technical feature when view over the prior art, they do not have a single inventive concept and so lack unity of invention. In addition, an application may properly be required to be restricted to one of two or more claimed inventions if they are able to support separate patents. The Examiner has shown that the Groups I-V are different inventions for the reasons in the previous Office action (see Paper mailed on May 12, 2025). The search and examination of the plural inventions would impose a serious burden upon the Examiner because they are different inventions, which require different searches, analyses and examination.
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
The requirement is still deemed proper and is therefore made FINAL.
Claims 11, 13-16, 19-24, 26-30, 35-37 and 39 are canceled. Claims 1-10, 12, 17-18, 25, 31-34, 38 and 40 are pending in this application. Claims 12, 17-18, 25, 31-33, 38 and 40 are withdrawn with traverse (filed 11/12/2025) from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Upon reconsideration, the species election among miRNA-21, miRNA-132, miRNA-9, miRNA-221 and the species election between Lamp-Lamp-2 and RVG are withdrawn because the subject matter can be found in the same prior art reference. The subject matter to the extent of miRNA-21, miRNA-132, miRNA-9, miRNA-221 and lamp-2 and RVG is included and under examination in this office action. Applicant timely traversed the restriction (election) requirement in the reply filed on November 12, 2025.
Claims 1-10 and 34 are under examination with respect to miRNA, miRNA-21, miRNA-132, miRNA-9, miRNA-221, AAV1, astrocytes, rabies virus glycoprotein (RVG)/Lamp2 and traumatic peripheral nerve injury in this office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, provisional Application No. 62/916208 filed October 16, 2019, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The instant application claims “a composition comprising a glial-derived extracellular vesicle wherein the extracellular vesicle comprises one or more of the following miRNA, Adeno-associated virus (AAV), siRNA,vRNA, mRNA, IncRNA, DNA…..combinations thereof including miRNA 21…miR-873a-5p, AAV1…AAVrh10…GFAP or combinations thereof” recited in claims 1-2 and 6, “wherein the glial-derived extracellular vesicle comprises a genetically modified protein or fragment thereof…” recited in claims 7-9, “wherein the extracellular vesicle has a diameter from about 10nm to about 1000nm” recited in claim 10 and a composition comprising a glial derived extracellular vesicle, wherein the extracellular vesicle comprises one or more gene editing tools….a ribonucleoprotein” recited in claim 34, which are not presented in the provisional Application No. 62/916208 filed 10/16/2019. The claimed composition comprising specific miRNA or AAV and other molecules recited in instant claims was only disclosed in the PCT Application No. PCT/US2020/056092 filed on October 16, 2020 (see claims 1-40 and p.1-6 of the specification of PCT/US2020/056092).
Therefore, the priority for the claimed subject matter in the instant application is October 16, 2020.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because of the following informalities: The use of the term“ExoGlow-protein” (p.47); “NanoSight”, “mTeSR1” (p. 54);“Accutase”, “Matrigel”, “Glutamax” (p. 54-55); “BrainPhys”, “Vetashield” (p.56), “Alexafluor-594”, “Alexafluor-488”, “Alexafluor-647”, “ExoGlow-protein” “ExoQuick-TC” (p. 57) “ which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required.
Claim Objections
Claims 1-2, 6 and 8 are objected to because of the following informalities:
i. The limitation “one or more of the following miRNA, an adeno-associated virus (AAV)…..or combinations thereof” recited in claim 1 should be “one or more of the following: miRNA, an adeno-associated virus (AAV)… or combinations thereof”. Appropriate correction is required.
ii. The recitations “vRNA” “IncRNA” recited in claim 1, “miRNA-21, miRNA-132, miRNA-9, miRNA-27a, miRNA-221, miRNA-200a-3p, miRNA-361, miRNA-274, miR-873a-5p” and “GFAP” recited in claim 2, “AAVDJ8” recited in claims 2 and 6, and “LFA-1”, “Mac-1”, “Vti-1A and B”, “CXCR4”, “FcR”, “GluR2/3”, “HLA-DM”, “MHC-1”, “MHC-2” and “TCR beta” recited in claim 8 are not unique or common abbreviations in the art. Applicants are required to spell out “vRNA” “IncRNA”, “miRNA-21, miRNA-132, miRNA-9, miRNA-27a, miRNA-221, miRNA-200a-3p, miRNA-361, miRNA-274, miR-873a-5p” and “GFAP”, “LFA-1”, “Mac-1”, “Vti-1A and B”, “CXCR4”, “FcR”, “GluR2/3”, “HLA-DM”, “MHC-1”, “MHC-2” and “TCR beta” at the first usage. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2 and 4-5 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 2 and 4-5 are indefinite because:
i. Regarding claim 2, the terms “miRNA-21, miRNA-132, miRNA-9, miRNA-27a, miRNA-221, miRNA-200a-3p, miRNA-361, miRNA-274, miR-873a-5p” are recited in the claims without a reference to a precise sequence identified by a proper SEQ ID NO: or providing a full name for abbreviated names. Without identification of property or combination of properties which are unique to and, therefore, definitiveness of the instant recitations, the metes and bounds of the claims remain undetermined. Further, the use of laboratory designations only to identify a particular molecule renders the claims indefinite because different laboratories may use the same laboratory designations to define completely distinct molecules. The rejection can be obviated by amending the claims to specifically and uniquely identify “miRNA-21, miRNA-132, miRNA-9, miRNA-27a, miRNA-221, miRNA-200a-3p, miRNA-361, miRNA-274, miR-873a-5p”, for example, by SEQ ID NO. and function of “miRNA-21, miRNA-132, miRNA-9, miRNA-27a, miRNA-221, miRNA-200a-3p, miRNA-361, miRNA-274, miR-873a-5p”.
ii. Regarding claims 4-5, the limitation “The composition of claim 3, wherein the cells are…or mammalian stem cells” recited in claim 4 is indefinite because the cells recited in claim 3 (i.e. astrocytes, Schwann cells, oligodendrocytes, ependymal cells, microglia or satellite cells) are fully differentiated cells, and cannot be mammalian stem cells. Thus, the claim is indefinite. Claim 5 is indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-10 and 34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 1-10 are drawn to a composition comprising a glial-derived extracellular vesicle, wherein the glial-derived extracellular vesicle comprises one or more of the following: miRNA, an adeno-associated virus (AAV), siRNA, vRNA, mRNA, lncRNA, DNA, tetraspanins, amino acids, metabolites, signaling protein, chaperons, cytoskeletal proteins, enzymes or combinations thereof.
Claim 34 is drawn to a composition comprising a glial-derived extracellular vesicle, wherein the glial-derived extracellular vesicle comprises one or more of gene editing tools, wherein the gene editing tools include a gene editing protein, an RNA molecule and/or a ribonucleoprotein.
The claims 1-10 encompass a genus of glial-derived extracellular vesicle comprising a genus of miRNA, AAV, siRNA, vRNA, mRNA, lncRNA, DNA, tetraspanins, amino acids, metabolites, signaling protein, chaperons, cytoskeletal proteins, enzymes or combinations thereof. The claim 34 encompasses a genus of glial-derived extracellular vesicle comprising a genus of gene editing tools comprising a genus of gene editing protein, a genus of RNA molecule and/or a genus of ribonucleoprotein.
Applicant has not disclosed sufficient species for the broad genus of glial-derived extracellular vesicle comprising a genus of miRNA, an adeno-associated virus (AAV), siRNA, vRNA, mRNA, lncRNA, DNA, tetraspanins, amino acids, metabolites, signaling protein, chaperons, cytoskeletal proteins, enzymes or combinations thereof or the broad genus of glial-derived extracellular vesicle comprising a genus of gene-editing tools comprising a genus of gene editing protein, a genus of RNA molecule and/or a genus of ribonucleoprotein.
The specification only describes isolation of extracellular vesicles (EV) from cultured human astrocytes that are positive for two glial cell specific markers: GFAP and S100B (astrocyte-derived extracellular vesicles) (Example 2) and cultured cortical neurons treated with astrocyte-derived extracellular vesicles (Examples 3-4).
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. From the specification, Applicant is in possession of astrocyte-derived extracellular vesicles isolated from cultured human astrocytes that are GFAP+ and S100B+. Based on US10962555, the contents, mRNAs and proteins of extracellular vesicles or exosomes isolated from different cells that express different markers and that are cultured under different conditions are different. For example, the astrocytes-derived extracellular vesicles isolated from GFAP+ and S100B+ astrocytes comprise miRNA-21, miRNA-132, miRNA-27 (see col. 13 in US10962555). However, Applicant is not in possession of the genus of exosomes/extracellular derived from all types of glial cells comprising all forms of miRNA, an adeno-associated virus (AAV), siRNA, vRNA, mRNA, lncRNA, DNA, tetraspanins, amino acids, metabolites, signaling protein, chaperons, cytoskeletal proteins, enzymes or combinations recited in instant claims.
The specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of glial cell-derived extracellular vesicles/exosomes. There is no description of the specific features and conserved regions which are critical to the function of the claimed genus of all forms of glial cell-derived extracellular vesicles/exosomes.
The specification provides no well-established structural and functional relationship between the astrocyte-derived extracellular vesicles (EV) isolated from cultured human astrocytes that are GFAP+ and S100B+ and the claimed genus of glial cell-derived extracellular vesicles/exosomes.
The specification also provides no well-established structural and functional relationship between the contents of the astrocyte-derived extracellular vesicles (EV) isolated from cultured human astrocytes that are GFAP+ and S100B+ as shown in US10962555 and the contents of the claimed genus of glial cell-derived extracellular vesicles/exosomes as recited in instant claims.
The specification also provides no well-established structural and functional relationship between the exosomes/extracellular vesicles comprising CRISPR-Cas9 system disclosed in Lin et al. (Adv. Sci. 2018; 5:1700611 cited in the 103 rejection) and the broad genus of glial-derived extracellular vesicle comprising a genus of gene-editing tools comprising a genus of gene editing protein, a genus of RNA molecule and/or a genus of ribonucleoprotein.
Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other glial-derived extracellular vesicles might be, what other contents in other glial-derived extracellular vesicles might be and what other glial-derived extracellular vesicle comprising a genus of gene-editing tools comprising a genus of gene editing protein, a genus of RNA molecule and/or a genus of ribonucleoprotein might be. Since the common characteristics/features of other glial-derived extracellular vesicles and their contents are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of glial-derived extracellular vesicles and their contents and the genus of glial-derived extracellular vesicle comprising a genus of gene-editing tools comprising a genus of gene editing protein, a genus of RNA molecule and/or a genus of ribonucleoprotein.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of glial-derived extracellular vesicles and their contents and the genus of glial-derived extracellular vesicle comprising a genus of gene-editing tools comprising a genus of gene editing protein, a genus of RNA molecule and/or a genus of ribonucleoprotein, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed glial-derived extracellular vesicles and their contents and the genus of glial-derived extracellular vesicle comprising a genus of gene-editing tools comprising a genus of gene editing protein, a genus of RNA molecule and/or a genus of ribonucleoprotein have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 7 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pusic et al. (US2019/0160097, May 30, 2019, priority Aug 15, 2012, as in IDS)
Claims 1-4, 7 and 10 are drawn to a composition comprising a glial-derived extracellular vesicle, wherein the glial-derived extracellular vesicle comprises one or more of the following: miRNA, an adeno-associated virus (AAV), siRNA, vRNA, mRNA, lncRNA, DNA, tetraspanins, amino acids, metabolites, signaling protein, chaperons, cytoskeletal proteins, enzymes or combinations thereof.
Pusic et al. (US2019/0160097) teach a composition comprising glial-derived extracellular vesicles including astrocyte-derived exosomes/extracellular vesicles, oligodendrocyte-derived exosomes/extracellular vesicles, and microglia-derived exosomes/extracellular vesicles, and wherein the glial-derived extracellular vesicles comprise miRNA, mRNA, DNA, cytoskeletal proteins, enzymes (see para.[0014];[0016]; [0023]-[0030]; [0085]; [0099]-[0105]). Pusic teaches different miRNA including miRNA-21, miRNA-9, miRNA-27a (see para. [0099]-[0105]; [0110]; [0116]; [0166]), GFAP (see para. [0066]) as in claim 2. Pusic teaches glial-derived extracellular vesicles derived from astrocytes, glial cells, microglia, or oligodendrocytes in 2D or 3D cultures as in claim 3 (see para.[0016]; [0066]; [0085]; [00203]-[00204]), which are primary mammalian cells as in claim 4. Pusic teaches that exosomes/extracellular vesicles/exosomes comprising a genetically modified protein or fragment thereof for expressing the protein or fragment thereof on the surface of the extracellular vesicle as in claim 7 (para. [0093]-[0094]). Pusic teaches that the extracellular vesicle has a diameter of about 1nm…1000nm or 40-100nm, which meets the claimed range of 10nm-1000nm as in claim 10 (see para. [0029]; [0080]). Thus, Claims 1-4, 7 and 10 are anticipated by Pusic et al. (US2019/0160097).
Claim Rejections - 35 USC § 102
13. Claims 1-4 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Goetzl et al. (US10962555, issued Mar 30, 2021, priority Jan 7, 2016) as evidenced by Pusic (US2019/0160097).
Goetzl et al. (US10962555) teach a composition comprising glial-derived extracellular vesicles including astrocyte-derived exosomes/extracellular vesicles, oligodendrocyte-derived exosomes/extracellular vesicles, and microglia-derived exosomes/extracellular vesicles, and wherein the glial-derived extracellular vesicles comprise miRNA, mRNA, DNA, cytoskeletal proteins, enzymes as in claim 1 (see col.15, lines 1-3; col. 14, line 55-col. 15, lines 58). Goetzl teaches different miRNA including miRNA-2 (col. 13, lines 38-46), GDNF (col.15, line 38), BDNF (Table 1) as in claim 2. Goetzl teaches glial-derived extracellular vesicles derived from astrocytes, Schwann cells, oligodendrocytes in 2D cultures as in claim 3 (col. 15, lines 1-3) which are primary mammalian cells as in claim 4. Goetzl teaches that the extracellular vesicle has a diameter of about 10nm-1000nm as in claim 10 as evidenced by Pusic (US2019/0160097; see para. [0029]; [0080]). Thus, claims 1-4 and 10 are being anticipated by Goetzl et al. (US10962555) as evidenced by Pusic (US2019/0160097).
Claim Rejections - 35 USC § 102
14. Claims 1-5 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sison et al. (Human Mol. Genet. 2017; 26:3409-3420. Doi:10.1093/hmg/ddx230).
Sison et al. teach exosomes/extracellular vesicles that are isolated from SMA astrocytes differentiated from induced pluripotent stem cells (iPSC-derived astrocytes) as recited in claims 1 and 4-5, wherein the iPSCs-derived astrocyte-derived exosomes/extracellular vesicles comprise miR-9, miR-100, miR-335, miR-375, miR431, miR-181a, miR-146a as in claim 2, and wherein the iPSC-derived astrocyte are in 2D cultures as in claim 3 (p. 3411-3413; p.3415-3416), which meet the limitations recited in claims 1-5 and 10. The iPSC-derived astrocyte-derived exosomes/extracellular vesicles have a diameter of about 10nm-1000nm as in claim 10 as evidenced by Pusic (US2019/0160097; see para. [0029]; [0080]). Thus, claims 1-5 and 10 are being anticipated by Sison as evidenced by Pusic (US2019/0160097).
Claim Rejections - 35 USC § 103
15. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Pusic (US2019/0160097), Goetzl (US10962555) or Sison (2017) in view of Liu et al. (Sci. Rep. 2015; 5:17543. DOI:10.1038/srep17543).
Pusic, Goetzl and Sison are set forth above but fails to teach that the exosomes/extracellular vesicles comprise a genetically modified protein or fragment thereof for expressing the protein or fragment thereof on the surface of the exosomes/extracellular vesicles, and wherein the genetically modified protein comprise Lamp-1/2 and/or at least one RVG protein as in claim 7-9.
Liu et al. teach modifying exosomes/extracellular vesicles to express a neuron-specific RVG protein on the membrane surface to deliver opioid receptor mu(MOR) siRNA, and wherein the modified exosomes/extracellular vesicles comprise a genetically modified protein: RVG-Lamp2b for expressing the RVG-Lamp2b on the surface of the exosomes/extracellular vesicles, which meets the limitation recited in claim 7-9 (see abstract; p.8, transfection and preparation of exosomes).
A person of ordinary skill in the art would have recognized that selecting and applying the known technique of modifying exosomes/extracellular vesicles by transfecting RVG/Lamp1/2b into cells to the astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl or Sison would have yielded the predictable result of astrocyte-derived exosomes/extracellular vesicles comprising a genetically modified protein or fragment thereof for expressing the protein or fragment thereof on the surface of the exosomes/extracellular vesicles, and wherein the genetically modified protein comprise Lamp-1/2 and/or at least one RVG protein and resulted in an improved product for better delivery of therapeutic agents by exosomes/extracellular vesicles and the use of astrocyte-derived exosomes/extracellular vesicles for pharmaceutical or therapeutic purposes.
Using the technique of modifying exosomes/extracellular vesicles to express a neuron-specific RVG protein on the membrane surface to deliver a therapeutic agent or a cargo in the astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl or Sison would generate comprising a genetically modified protein or fragment thereof for expressing the protein or fragment thereof on the surface of the exosomes/extracellular vesicles, and wherein the genetically modified protein comprise Lamp-1/2 and/or at least one RVG protein, and expand application of the astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl or Sison for pharmaceutical and therapeutic purposes, and would increase patient’s satisfaction with treatment using astrocyte-derived exosomes/extracellular vesicles because the modified astrocyte-derived exosomes/extracellular vesicles expressing RVG protein/Lamp-1/2 provide better delivery of the astrocyte-derived exosomes/extracellular vesicles and their cargos/therapeutic agents.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known technique of modifying exosomes/extracellular vesicles by transfecting RVG/Lamp1/2b into cells to the astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl or Sison and yield the predictable result of astrocyte-derived exosomes/extracellular vesicles comprising a genetically modified protein or fragment thereof for expressing the protein or fragment thereof on the surface of the exosomes/extracellular vesicles, and wherein the genetically modified protein comprise Lamp-1/2 and/or at least one RVG protein for better delivery of therapeutic agents by exosomes/extracellular vesicles and/or the use of astrocyte-derived exosomes/extracellular vesicles for pharmaceutical or therapeutic purposes.
Claim Rejections - 35 USC § 103
16. Claims 2, 6 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Pusic (US2019/0160097), Goetzl (US10962555) or Sison (2017) in view of Liu et al. (2015) as applied to claims 7-9 above and further in view of Lin et al. (Adv. Sci. 2018; 5:1700611. DOI:10.1002/advs.201700611).
Pusic, Goetzl, Sison and Liu are set forth above but fail to teach different AAV1, AAV2, AAV5,AAV6, AAV9, AAVDJB and AAVrh10 as in claims 2 and 6 or a composition comprising a glial-derived extracellular vesicle comprising one or more gene editing tools including a gene editing protein, an RNA molecule and/or a ribonucleoprotein as in claim 34.
Lin et al. teach a composition comprising exosome-liposomes comprising gene editing tools including the CRISPR-Cas9 system for manipulating differentiation of mesenchymal stem cells or delivery of a therapeutic agent, wherein the CRISPR-Cas9 system comprises adeno-associated virus (AAV) vector including different AAV1-10, a gene editing protein, an RNA molecule and/or a ribonucleoprotein: sgRNA-Cas9 (p. 3-8, Figures 4-5; p. 6-8, Experimental section).
A person of ordinary skill in the art would have recognized that selecting and applying the known technique of exosomes/extracellular vesicles comprising one or more gene editing tools including CRISPR-Cas9 system including a gene editing protein, an RNA molecule and/or a ribonucleoprotein to the astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl or Sison or to the modified astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl, Sison and Liu would have yielded the predictable result of a composition comprising a glial-derived extracellular vesicle comprising one or more gene editing tools including the CRISPR-Cas9 system including a gene editing protein, an RNA molecule and/or a ribonucleoprotein, and resulted in an improved product for manipulating differentiation of mesenchymal stem cells or delivery of a therapeutic agent for pharmaceutical and therapeutic purposes.
Using and including the known technique of exosomes/extracellular vesicles comprising one or more gene editing tools including CRISPR-Cas9 system including a gene editing protein, an RNA molecule and/or a ribonucleoprotein in the astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl or Sison or to the modified astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl, Sison and Liu would generate the claimed composition comprising the claimed glial-derived extracellular vesicle comprising one or more gene editing tools including a gene editing protein, an RNA molecule and/or a ribonucleoprotein a glial-derived extracellular vesicle comprising one or more gene editing tools including a gene editing protein, an RNA molecule and/or a ribonucleoprotein, and expand application of the astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl or Sison or to the modified astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl, Sison and Liu, and would increase patient’s satisfaction with treatment using the astrocyte-derived exosomes/extracellular vesicles because the exosomes/extracellular vesicles comprising one or more gene editing tools including CRISPR-Cas9 system including a gene editing protein, an RNA molecule and/or a ribonucleoprotein provide options for manipulating differentiation of mesenchymal stem cells or delivery of a therapeutic agent.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known technique of exosomes/extracellular vesicles comprising one or more gene editing tools including CRISPR-Cas9 system including a gene editing protein, an RNA molecule and/or a ribonucleoprotein to the astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl or Sison or to the modified astrocyte-derived exosomes/extracellular vesicles of Pusic, Goetzl, Sison and Liu, and yield the predictable result of a composition comprising glial-derived exosomes/extracellular vesicles comprising gene editing tools including the CRISPR-Cas9 system for manipulating differentiation of mesenchymal stem cells or delivery of a therapeutic agent, wherein the CRISPR-Cas9 system comprises an adeno-associated virus (AAV) vector including different AAV1-10, a gene editing protein, an RNA molecule and/or a ribonucleoprotein: sgRNA-Cas9.
Conclusion
17. NO CLAIM IS ALLOWED.
18. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Stice et al. (US11993787) teach a composition comprising neural extracellular vesicles (EVs) and methods of use for treatment of neurodegenerative diseases including spinal cord injury, stroke other neurodegenerative diseases, wherein the neural extracellular vesicles are isolated from neural progenitor cells produced from pluripotent stem cells, embryonic stem cells or induced pluripotent stem cells or PSC-derived neural cells including glial cells, astrocytes, oligodendrocytes (col.1, line 51-col.2, line 11), and wherein the composition further comprises one or more agents including neurotrophic factor, BDNF, GDNF, CNTF (col.2, line 60-col.3, line 25, claims 1-14).
Dickens et al. (Sci. Signal.2017; 10:eaa17696.p. 1-12) teaches astrocyte-derived extracellular vesicles or GFAP-EGFP astrocyte-derived extracellular vesicles comprising perioxisome proliferator-activated receptor alpha (PPARa) (p.1, abstract; p.5-7).
Hyung et al. (Immunotherapy, 2019; 5:156. Doi:10.35248/2471-9552.19.5.156) teaches Schwann cell-derived exosomes/extracellular vesicles (see p.1).
Zheng et al. (Bioconjugate Chem. 2019; 30:994-1005) teach the use of exosomes/extracellular vesicles for brain drug delivery, and wherein the exosomes/extracellular vesicles can be modified to cross the BBB including lamp2/RVG peptide (p. 998; p. 1000-1001).
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Chang-Yu Wang
March 7, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675